Heart rate indicated atrioventricular delay optimization

ABSTRACT

Systems and methods for monitoring and treating patients with heart failure are discussed. The system can store in a memory stimulation parameters, including stimulation timing parameters for a plurality of heart rate ranges. The system includes a plurality of timers with respective durations for the plurality of heart rate ranges. A stimulation control circuit can identify a target heart range in which a detected heart rate falls, and measure an atrioventricular (AV) conduction characteristic value in response to the timer for the target heart range being expired at the detected heart rate. The stimulation control circuit can update a stimulation parameter corresponding to the target heart rate range using the measured AV conduction characteristic. The updated stimulation parameter can be used in cardiac stimulation.

CLAIM OF PRIORITY

This application claims the benefit of priority under 35 U.S.C. § 119(e)of U.S. Provisional Patent Application Ser. No. 62/779,792, filed onDec. 14, 2018, which is herein incorporated by reference in itsentirety.

TECHNICAL FIELD

This document relates generally to medical systems and devices, and moreparticularly, to systems, devices, and methods of electrostimulation fortreating heart failure.

BACKGROUND

Congestive heart failure (CHF) is a leading cause of death in the UnitedStates and globally. CHF occurs when the heart is unable to adequatelysupply enough blood to maintain a healthy physiological state. CHF maybe treated by drug therapy, or by electrostimulation therapy.

Implantable medical devices (IMDs) have been used to monitor CHFpatients and manage heart failure in an ambulatory setting. Some IMDsmay include sensors to sense physiological signals from a patient, anddetect worsening heart failure, such as heart failure decompensation.Frequent patient monitoring and early detection of worsening heartfailure may help improve patient outcome. Identification of patient atan elevated risk of future heart failure events may help provide timelytreatment and prevent or reduce hospitalization. Identifying and safelymanaging the patients at risk of worsening heart failure can avoidunnecessary medical interventions, hospitalization, and reducehealthcare cost.

An IMD may include a pulse generator and electrical circuitry configuredto electrically stimulate a heart or other excitable tissue, to helprestore or improve the cardiac performance, or to correct cardiacarrhythmias. One example of the electrostimulation therapy is cardiacresynchronization therapy (CRT). CRT, typically delivered asbiventricular (BiV) pacing or synchronized left ventricle (LV)-onlypacing, may be indicated for CHF patients with moderate to severesymptoms and ventricular dyssynchrony. CRT keeps the LV and rightventricle (RV) pumping synchronously by sending electrical stimuli toboth the LV and RV. The synchronized stimulation may improve heartpumping efficiency and increase blood flow in some CHF patients. CRT candecrease hospitalization and morbidity associated with worsening heartfailure, as well as improvements in quality of life.

SUMMARY

This document discusses, among other things, a patient management systemfor monitoring and treating patients with heart failure. The system maystore in a memory a set of stimulation parameters, including stimulationtiming parameters for a plurality of heart rate ranges. The system mayinclude respective timers for the plurality of heart rate ranges. Astimulation control circuit can program the timers with respectivedurations, identify from the plurality of heart rate ranges a targetheart range in which a detected heart rate falls, and measure anatrioventricular (AV) conduction characteristic value in response to thetimer for the target heart range being expired at the detected heartrate. The stimulation control circuit can update a stimulationparameter, corresponding to the target heart rate range, using themeasured AV conduction characteristics. The updated stimulationparameter can be used for cardiac pacing.

Example 1 is a medical-device system, comprising a stimulation controlcircuit configured to generate a control signal to deliver cardiacstimulation to a heart of a patient according to stimulation parametersstored in a memory according to a plurality of heart rate ranges, and toupdate at least a portion of the stored stimulation parameters. Theupdate of a portion of the stimulation parameters include: provide aplurality of timers each having a duration, wherein each of theplurality of timers corresponds to different heart rate ranges, and isconfigured to expire after the respective duration has elapsed from arespective reset time; identify, from the plurality of heart rateranges, a target heart range in which a detected heart rate falls, andmeasure an atrioventricular conduction characteristic value if the timerfor the target heart range has expired at the detected heart rate; andupdate at least a portion of the stimulation parameters stored in thememory and corresponding to the target heart rate range using themeasured atrioventricular conduction characteristic.

In Example 2, the subject matter of Example 1 optionally includes thestimulation control circuit that can be configured to reset the timerfor the target heart rate range upon measuring the atrioventricularconduction characteristic value.

In Example 3, the subject matter of any one or more of Examples 1-2optionally includes the stimulation control circuit that can beconfigured to select a stimulation parameter value from the set of thestimulation parameters for a detected heart rate. The system cancomprise a stimulator circuit configured to deliver cardiac stimulationusing the selected stimulation parameter value.

In Example 4, the subject matter of any one or more of Examples 1-3optionally includes the stimulation timing parameters that can includeatrioventricular delay (AVD) values.

In Example 5, the subject matter of any one or more of Examples 1-4optionally includes the atrioventricular conduction characteristic thatcan include intrinsic atrioventricular interval (AVI), and thestimulation control circuit can be configured to generate a controlsignal to suspend ventricular stimulation during the measurement ofintrinsic AVI and to resume ventricular stimulation after themeasurement of intrinsic AVI.

In Example 6, the subject matter of any one or more of Examples 1-5optionally includes the stimulation control circuit that can beconfigured to generate, in response to the measurement of anatrioventricular conduction characteristic, a control signal to disableany subsequent measurement of atrioventricular conduction characteristicduring a blanking period.

In Example 7, the subject matter of any one or more of Examples 1-6optionally includes the stimulation control circuit that can beconfigured to determine a stimulation parameter for the target heartrate range using the measured atrioventricular conduction characteristicscaled a weight factor.

In Example 8, the subject matter of Example 7 optionally includes thestimulation control circuit that can be configured to update astimulation parameter for the target heart rate range using a weightedcombination of a historical stimulation timing parameter value and themeasured atrioventricular conduction characteristic each scaled byrespective weight factors.

In Example 9, the subject matter of any one or more of Examples 1-8optionally includes a global timer having a duration, and thestimulation control circuit is configured to update at least the portionof the stimulation parameters in response to an expiration of the globaltimer.

In Example 10, the subject matter of any one or more of Examples 1-9optionally includes the plurality of timers that can include a firsttimer for a first heart rate range, and a second timer for a secondheart rate range higher than the first heart rate range. The stimulationcontrol circuit can be configured to program the second timer with aduration shorter than a duration of the first timer.

In Example 11, the subject matter of any one or more of Examples 1-10optionally includes the stimulation control circuit that can beconfigured to determine or update the respective durations of theplurality of timers using information of prevalence of heart ratesdetected in the corresponding plurality of heart rate ranges.

In Example 12, the subject matter of any one or more of Examples 1-11optionally includes the stimulation control circuit that can beconfigured to store in the memory a stimulation parameter tableincluding the set of stimulation timing parameters and the correspondingplurality of heart rate ranges.

In Example 13, the subject matter of any one or more of Examples 1-12optionally includes the stimulation control circuit that can beconfigured to: generate, and store in the memory, a regression modelbetween (1) values of the atrioventricular conduction characteristiccorresponding to a plurality of heart rate ranges and (2) the pluralityof heart rate ranges; and estimate a value of the atrioventricularconduction characteristic at a specific heart rate using the generatedregression model.

In Example 14, the subject matter of any one or more of Examples 1-13optionally includes the stored set of stimulation parameters that canfurther correspond to atrial sensed (AS) events or atrial paced (AP)events at the plurality of heart rate ranges, and the stimulationcontrol circuit is configured to select the parameter for use duringcardiac stimulation using information of a AS or AP event.

In Example 15, the subject matter of any one or more of Examples 1-14optionally includes the stored set of stimulation parameters that canfurther include information of a pacing chamber configuration for aplurality of heart rate or heart rate ranges, the pacing chamberconfiguration including a left-ventricular (LV) only pacing or abi-ventricular (BiV) pacing of both left and right ventricles, whereinthe stimulation control circuit is configured to select the LV-onlypacing or the BiV pacing using an atrioventricular interval or anatrioventricular interval variability at a sensed heart rate.

Example 16 is a method of operating a medical-device system to controlcardiac stimulation using a plurality of timers corresponding to aplurality of heart rate ranges, each of the plurality of timersconfigured to expire after a respectively programmed duration haselapsed from a respective reset time. The method comprises steps of:monitoring patient heart rates; identifying, from the plurality of heartrate ranges, a target heart range in which a detected heart rate falls;measuring an atrioventricular conduction characteristic value if a timerfor the target heart range has expired at the detected heart rate; andupdating at least a portion of a set stimulation parameters stored in amemory and corresponding to the target heart rate range using themeasured atrioventricular conduction characteristic; wherein the set ofstimulation parameters include stimulation timing parameterscorresponding to the plurality of heart rate ranges.

In Example 17, the subject matter of Example 16 optionally includesstoring the set of stimulation parameters that can include storing inthe memory a stimulation parameter table that includes the stimulationtiming parameters for atrial sensed (AS) events or atrial paced (AP)events and corresponding to the plurality heart rate ranges.

In Example 18, the subject matter of any one or more of Examples 16-17optionally includes thee stimulation timing parameters that can includeatrioventricular delay (AVD) values. The atrioventricular conductioncharacteristic can include intrinsic atrioventricular interval (AVI).The method further comprises steps of generating a control signal tosuspend ventricular stimulation during the measurement of intrinsic AVI,and after the measurement of intrinsic AVI, resuming ventricularstimulation and resetting the timer for the target heart rate range.

In Example 19, the subject matter of any one or more of Examples 16-18optionally includes, subsequent to the measurement of intrinsic AVI,generating a control signal to disable any subsequent measurement ofintrinsic AVI during a blanking period.

In Example 20, the subject matter of any one or more of Examples 16-19optionally includes determining or updating the respective durations forthe plurality of timers using information of prevalence of heart ratesdetected in the corresponding plurality of heart rate ranges.

In Example 21, the subject matter of any one or more of Examples 16-20optionally includes updating at least a portion of the stimulationparameters includes using a weighted combination of a historicalstimulation timing parameter value and the measured atrioventricularconduction characteristic each scaled by respective weight factors.

In Example 22, the subject matter of any one or more of Examples 16-21optionally includes selecting a stimulation parameter value from the setof the stimulation parameters for a detected heart rate, and deliveringcardiac stimulation via a stimulator circuit using the selectedstimulation parameter value.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present invention isdefined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are illustrated by way of example in the figures ofthe accompanying drawings. Such embodiments are demonstrative and notintended to be exhaustive or exclusive embodiments of the presentsubject matter.

FIG. 1 illustrates an example of a patient management system andportions of an environment in which the system may operate.

FIG. 2 illustrates an example of a dynamically controlled cardiacstimulation system configured to program and deliver electrostimulationto treat HF or other cardiac diseases.

FIG. 3 is a block diagram illustrating an example of a heartrate-indicated AVI sampling control circuit configured to sample AVconduction characteristics for heart rates sensed in a plurality ofheart rate ranges.

FIG. 4 is a timing diagram illustrating an exemplary sequence of eventsduring sampling of AVI values and updating AVD for respective heart rateranges.

FIGS. 5A-5C are diagrams illustrating patient condition-indicatedstimulation parameter table stored in a memory that can be used fordynamic cardiac pacing.

FIG. 6 is a flow chart illustrating a method for updating a stimulationparameter and delivering cardiac stimulation using the updatedstimulation parameter.

FIG. 7 illustrates a block diagram of an example machine upon which anyone or more of the techniques (e.g., methodologies) discussed herein mayperform.

DETAILED DESCRIPTION

Ambulatory medical devices (AMDs), such as IMDs, subcutaneous medicaldevices, wearable medical devices, or other external medical devices,may be used to detect worsening heart failure and deliver heart failure(HF) therapy to restore or improve the cardiac function. An IMD may becoupled to implanted leads with electrodes that may be used to sensecardiac activity, or to deliver HF therapy, such as cardiac stimulation.An AMD may have functionality of programmable therapy that allows formanual or automatic adjustment of electrostimulation parameters, such asstimulation chamber or site, stimulation mode, or stimulation timing.

An AMD can be configured to stimulation various cardiac chambers torestore cardiac synchrony and improve hemodynamics. During CRT or BiVpacing, synchronized stimulation may be applied to the LV and the RV ofa heart. The RV and LV pacing sites may be stimulated concurrently, orsequentially with an RV-LV interventricular pacing delay (VVD). Deliveryof LV and RV pacing may be timed relative to a fiducial point, such asan intrinsic atrial depolarization sensed by an atrial electrode (atrialsense, or AS), or an atrial pacing pulse (AP) that elicits atrialactivation. If no intrinsic ventricular depolarization is detectedwithin a period of atrial-ventricular delay (AVD) following the AS orthe AP, the LV and RV pacing may be delivered at the end of the AVD.

In addition to BiV pacing, stimulation may be delivered only at oneheart chamber, such as the LV. The LV-only pacing may improve cardiacsynchrony in certain patients, such as those with intact AV conductionrequiring cardiac resynchronization. Compared to the BiV pacing, LV-onlypacing may require a simpler implantable procedure, consumes less power,and provides increased battery longevity. As such, it is clinically avalid alternative to more complicated BiV therapy regime. Similar totiming of BiV pacing, the LV pacing may be delivered at the end of aprogrammed AVD subsequent to the AS or the AP if no intrinsic LVdepolarization is detected within the period of AVD.

An AMD can be configured to stimulate one or more sites of a heartchamber simultaneously or sequentially. In conventional single sitepacing (SSP), only one site of a particular heart chamber (e.g., the LV)is stimulated. Alternatively, multisite pacing (MSP) can be used to asan alternative to SSP. The MSP involves electrostimulation at two ormore sites in a heart chamber within a cardiac cycle. For example, in LVMSP, multiple LV sites may be simultaneously stimulated, or separated byone or more intra-LV time offset (ILVD). MSP may improve LV function andhemodynamic responses in some patients. However, MSP may require moreenergy than SSP, and may also increase the complexity of system designand operation. Not all CHF patients can uniformly benefit more from MSPthan SSP.

A stimulation timing parameter, such as AVD, VVD, or ILVD discussedabove, defines a timing sequence of cardiac stimulation. Because suchtiming sequence may affect therapy efficacy and patient hemodynamicoutcome, proper selection or programming of a timing parameter can beimportant in HF management. For example, AVD can be determined usinginformation about patient intrinsic AV conduction characteristics, suchas an intrinsic AV interval (AVI) between a P wave and an R wave withina cardiac cycle in an electrocardiograph (ECG), or between an atrialsensed (AS) or atrial paced (AP) event to a ventricular sensed event(VS) within a cardiac cycle in an subcutaneously measured electrogram(EGM). In a patient, the intrinsic AVI may not stay constant, but varyunder a multitude of physiological or functional conditions. Forexample, long-term changes in patient health conditions, HF progressionssuch as remodeling or decompensation, or short-term changes in heartrate, postures, posture transitions, physical activities, sleep/awakestatus, medication, hydration, diet, among other factors, may affect theAVI. As a consequence of long-term or short-term variation in patient AVconduction characteristics, HF therapy (e.g., CRT, LV-only or BiVpacing, SSP or MSP) in accordance with a previously optimized AVD may nolonger be effective or optimal.

The present inventors have recognized several technical challenges incardiac pacing therapy for treating HF. One challenge has to do withindividualized and dynamic HF therapy to address inter-patientdifferences in cardiac pacing therapy efficacy, as well as intra-patientvariation over time in cardiac pacing efficacy at least due to long-termand short-term changes in patient physiological or functionalconditions. For example, patient cardiac status such as intrinsic AVconduction characteristics may vary at different heart rate or heartrate ranges. A HF therapy optimized based on patient prior conditions orat one heart rate range may not be optimal under a different conditionor heart rate range. Another challenge pertains to efficient acquisitionof information of patient cardiac status, such as intrinsic AVconduction characteristics, for use in optimizing individualized HFtherapy. A conventional technique for acquiring patient cardiac statusinformation includes monitoring a physiologic signal, and sampling aphysiologic parameter (e.g., an AV conduction characteristic) at apredetermined fixed time interval or rate. In this document, thesampling of a physiologic parameter refers to measuring the physiologicparameter according to a schedule, such as at a particular time or aperiodic sampling rate (e.g., performing a measurement once every 5minutes). For example, intrinsic AVI can be sampled once per minute. Atherapy parameter, such as AVD, can be adjusted accordingly using thesampled AVI value. Conventional periodic sampling at a fixed interval orrate may have several disadvantages. First, in some instances, it maynot effectively capture the changes in patient cardiac condition. Forexample, although HF patients may have their heart rates more frequentlyhovering within a relatively narrow range (hereinafter referred to as“frequent heart rates,” e.g., 50-80 bpm) due to their impaired cardiacfunctional capacity, other heart rates (hereinafter referred to as “rareheart rates,” e.g., >100 bpm) may occasionally occur under certaincircumstances. The heart rate can include intrinsic heart rates in theabsence of atrial pacing. Alternatively, the heart rates can be detectedduring atrial pacing. Such atrial-paced heart rates are substantiallyequal to atrial pacing rates. To optimize HF therapy under differentcardiac status such as different heart rates, stimulation parameters canbe re-optimized for those “rare heart rates.” However, conventionalperiodic sampling at a fixed interval or rate may not reliably capturethe AV conduction characteristics corresponding to the “rare heartrates,” at least because the “rare heart rates” may occur outside thepredetermined sampling intervals. Instead, the sampled AV conductioncharacteristics may likely correspond to “frequent heart rates.” Thismay not only prevent or delay therapy re-optimization for the “rareheart rates,” but can waste system resources and battery power due tounintended repetitive sampling of AV conduction characteristics for the“frequent heart rates.”

Another challenge pertains to a guarantee of adequate ventricular pacingtherapy (e.g., CRT). During a therapy optimization process, pacingtherapy may have to be suspended, albeit temporarily, so as to provideevent sensing and evaluation of intrinsic AV conduction characteristics.Frequent suspension of pacing for AVI reevaluation may adversely affectpatient outcome, particularly in pacing-dependent patients. With regardto the conventional periodic sampling at a fixed interval or rate,although increasing the rate (or, decreasing the interval) of periodicsampling of AV conduction characteristic may increase the likelihood ofcapturing the “rare heart rates,” it may increase the pacing suspensiontime substantially. For example, by increasing the sampling rate fromonce per minute to once per 30 seconds, the pacing suspension time canbe doubled. This may be clinically impactful to pacing-dependentpatients. Moreover, the higher sampling rate may result in substantiallymore repetitive sampling and processing the AV conductioncharacteristics for the “frequent heart rates,” exacerbating inefficientsystem resource use and wasting battery power.

The present document provides technical solutions to theabove-identified challenges in cardiac pacing therapy for HF, and canimprov the medical technology of device-based heart failure patientmanagement. Among other things, the present document provides apparatusand methods for updating stimulation parameters, including stimulationtiming parameters such as AVD values corresponding to different heartrates or heart rate ranges. The dynamic parameter update discussedherein may also apply to other stimulation parameters, such as fordetermining a stimulation site or a stimulation mode. The dynamicparameter update can tailor cardiac pacing therapy to an individualpatient, as well as to particular patient physiological or functionalconditions. In some examples, the stimulation parameter values (e.g.,AVD) corresponding to a multitude of patient conditions may be arrangedin a stimulation parameter table. Adjustment of stimulation timing,stimulation site, or stimulation mode based on patient conditions mayhelp tailor cardiac pacing therapy to individual patient under specificphysiologic conditions. In an example, the dynamic adjustment may bespecific to a heart rate or heart rate range, or on a beat-to-beatbasis. In addition to improved therapy efficacy and patient outcome, thesystems and methods discussed herein may also reduce healthcare costassociated with HF management. The present document also providesidentification of the conditions that may affect stimulation timing andtherapy efficacy. This may be beneficial for healthcare providers totrack patient HF progression, and improve patient management.

This document also discusses a timing control technique to time AVconduction characteristic measurement for heart rates falling indifferent heart rate ranges. In an embodiment, separate timers may beprovided for a plurality of heart rate ranges, and independently time AVconduction characteristic measurement (e.g., enabling or disabling thesampling AV conduction characteristic) for the corresponding heart rateranges. When a heart rate (intrinsic heart rate, or heart rate duringatrial pacing) is detected in a particular heart rate range, the AVconduction characteristic can be measured only when the timer,corresponding to the particular heart rate range, times out. The timerscan each be programmed with a respective timer duration. The timers canoperate independently, with their own reset time and expiration time.When a first timer blocks sampling AV conduction characteristic for asensed heart rate falling in a first heart rate range, a second timermay still enable sampling AV conduction characteristic for a sensedheart rate falling in a different second heart rate range. Because the“rare heart rates” in HF patients are typically in a different heartrate range than the “frequent heart rates,” separate timers can time thesampling of the AV conduction characteristics for the “rare heart rates”and for “frequent heart rates” respectively. Compared to conventionalperiodic sampling at a fixed interval or rate irrespective of heartrates, the multiple timers for different heart rate ranges as discussedin this document can more reliably capture patient AV conductioncharacteristics for the “rare heart rates.” Additionally, because thesampling of AV conduction characteristic for the “frequent heart rates”is timing-controlled by a timer dedicated to that heart rate range, therepetitive sampling of AV conduction characteristics for the “frequentheart rates” can be substantially reduced. Accordingly, system resourcesand battery power can be saved, and overall operation cost can bereduced.

In addition to the improvement in the medical technology of device-basedheart failure patient management under various patient conditions, thesystems, devices, and methods discussed herein may also allow for moreefficient device memory usage, such as by storing and updating thestimulation timing parameter that are clinically more relevant topatient long-term and short-term changing conditions. The individualizedand dynamically adjusted therapy discussed in this document may not onlyimprove therapy efficacy and patient outcome, but may also save devicepower and extend battery life. With individualized HF therapy tailoredto specific patient conditions, fewer unnecessary interventions orhospitalizations may be scheduled, prescribed, or provided; as a result,overall cost savings may be realized.

FIG. 1 illustrates an example of a patient management system 100 andportions of an environment in which the patient management system 100may operate. The patient management system 100 may include an ambulatorymedical device, such as an implantable medical device (IMD) 110 that maybe electrically coupled to a heart 105 through one or more leads 108A-C,and an external system 120 that may communicate with the IMD 110 via acommunication link 103. Examples of the IMD 110 may include, but are notlimited to, pacemakers, defibrillators, cardiac resynchronizationtherapy (CRT) devices, cardiac remodeling control therapy (RCT) devices,neuromodulators, drug delivery devices, biological therapy devices,diagnostic devices such as cardiac monitors or loop recorders, orpatient monitors, among others. The IMD 110 may be coupled to, or may besubstituted by a monitoring medical device such as a bedside or otherexternal monitor. In addition to or in lieu of the IMD 110, otherambulatory medical device may be used, which may include subcutaneousmedical device such as a subcutaneous monitor or diagnostic device, orexternal monitoring or therapeutic medical devices such as automaticexternal defibrillators (AEDs) or Holter monitors; wearable medicaldevices such as patch-based devices, smart watches, or smartaccessories; or a bedside monitor.

The IMD 110 may include a hermetically sealed can 112 that may house anelectronic circuit that may sense a physiological signal in the heart105 and may deliver one or more therapeutic electrical pulses to atarget region, such as in the heart, such as through one or more leads108A-C. The patient management system 100 may include only one lead suchas 108B, or may include two leads such as 108A-B.

The lead 108A may include a proximal end that may be connected to IMB110 and a distal end that may be placed at a target location such as inthe right atrium (RA) 131 of the heart 105. The lead 108A may have afirst pacing-sensing electrode 141 that may be located at or near itsdistal end, and a second pacing-sensing electrode 142 that may belocated at or near the electrode 141. The electrodes 141 and 142 may beelectrically connected to the IMB 110 such as via separate conductors inthe lead 108A, such as to allow for sensing of the right atrial activityand optional delivery of atrial pacing pulses. The lead 108B may be adefibrillation lead that may include a proximal end that may beconnected to IMD 110 and a distal end that may be placed at a targetlocation such as in the right ventricle (RV) 132 of heart 105. The lead108B may have a first pacing-sensing electrode 152 that may be locatedat distal end, a second pacing-sensing electrode 153 that may be locatednear the electrode 152, a first defibrillation coil electrode 154 thatmay be located near the electrode 153, and a second defibrillation coilelectrode 155 that may be located at a distance from the distal end suchas for superior vena cava (SVC) placement. The electrodes 152 through155 may be electrically connected to the IMD 110 such as via separateconductors in the lead 108B. The electrodes 152 and 153 may allow forsensing of a ventricular EGM and may optionally allow delivery of one ormore ventricular pacing pulses, and electrodes 154 and 155 may allow fordelivery of one or more ventricular cardioversion/defibrillation pulses.In an example, the lead 108B may include only three electrodes 152, 154and 155. The electrodes 152 and 154 may be used for sensing or deliveryof one or more ventricular pacing pulses, and the electrodes 154 and 155may be used for delivery of one or more ventricular cardioversion ordefibrillation pulses. The lead 108C may include a proximal end that maybe connected to the IMB 110 and a distal end that may be placed at atarget location such as in a left ventricle (LV) 134 of the heart 105.The lead 108C may be implanted through the coronary sinus 133 and may beplaced in a coronary vein over the LV such as to allow for delivery ofone or more pacing pulses to the LV. The lead 108C may include anelectrode 161 that may be located at a distal end of the lead 108C andanother electrode 162 that may be located near the electrode 161. Theelectrodes 161 and 162 may be electrically connected to the IMB 110 suchas via separate conductors in the lead 108C such as to allow for sensingthe LV EGM and optionally allow delivery of one or moreresynchronization pacing pulses from the LV. Additional electrodes maybe included in or along the lead 108C. In an example, as illustrated inFIG. 1, a third electrode 163 and a fourth electrode 164 may be includedin the lead 108. In some examples (not shown in FIG. 1), at least one ofthe leads 108A-C, or an additional lead other than the leads 108A-C, maybe implanted under the skin surface without being within at least oneheart chamber, or at or close to heart tissue.

The IMB 110 may include circuitry that may sense a physiological signal.The physiological signal may include an EGM or a signal representingmechanical function of the heart 105. The hermetically sealed can 112may function as an electrode such as for sensing or pulse delivery. Forexample, an electrode from one or more of the leads 108A-C may be usedtogether with the can housing 112 such as for unipolar sensing of an EGMor for delivering one or more pacing pulses. A defibrillation electrodefrom the lead 108B may be used together with the can housing 112 such asfor delivering one or more cardioversion/defibrillation pulses. In anexample, the IMB 110 may sense impedance such as between electrodeslocated on one or more of the leads 108A-C or the can housing 112. TheIMB 110 can be configured to inject current between a pair ofelectrodes, sense the resultant voltage between the same or differentpair of electrodes, and determine impedance using Ohm's Law. Theimpedance may be sensed in a bipolar configuration in which the samepair of electrodes may be used for injecting current and sensingvoltage, a tripolar configuration in which the pair of electrodes forcurrent injection and the pair of electrodes for voltage sensing mayshare a common electrode, or tetrapolar configuration in which theelectrodes used for current injection may be distinct from theelectrodes used for voltage sensing. In an example, the IMD 110 can beconfigured to inject current between an electrode on the RV lead 108Band the can housing 112, and to sense the resultant voltage between thesame electrodes or between a different electrode on the RV lead 108B andthe can housing 112. A physiological signal may be sensed from one ormore physiological sensors that may be integrated within the IMD 110.The IMD 110 may also be configured to sense a physiological signal fromone or more external physiological sensors or one or more externalelectrodes that may be coupled to the IMD 110. Examples of thephysiological signal may include one or more of ECG, intracardiac EGM,heart rate, heart rate variability, intrathoracic impedance,intracardiac impedance, arterial pressure, pulmonary artery pressure,left atrial pressure, RV pressure, LV coronary pressure, coronary bloodtemperature, blood oxygen saturation, one or more heart sounds, physicalactivity or exertion level, physiological response to activity, posture,respiration, body weight, or body temperature, among others.

In certain examples, the system 100 may include one or more leadlesssensors not being tethered to the IMD 110 via the leads 108A-C. Theleadless ambulatory sensors can be configured to sense a physiologicalsignal and wirelessly communicate with the IMD 110. In some examples,the IMD 110 may be a leadless medical device. Unlike a tethered devicesuch as the IMD 110 as illustrated in FIG. 1, a leadless medical devicerequires no lead, wire, or tether extended between the electrodes andthe device body. The leadless medical device may include an anchoring orfixation mechanism for positioning the device body on a target implantside, such as an endocardial surface of one of a left ventricle, a rightventricle, a left atrium, or a right atrium, or an epicardial surface ofa portion of the heart. The leadless medical device may be deliveredtransvenously and positioned within a blood vessel on the heart, such asa coronary vein, where one or more electrodes on the leadless medicaldevice may be directly or indirectly in contact with the epicardialsurface of the heart. An example of such an leadless medical device mayinclude the leadless cardiac pacemaker (LCP) disclosed in the commonlyassigned U.S. Patent Application Publication US2016/0051823 by Maile etal., entitled “LEADLESS CARDIAC PACEMAKER HAVING A SENSOR WITH A LOWERPOWER MODE,” which is hereby incorporated by reference in its entirety.

The arrangement and functions of these leads and electrodes aredescribed above by way of example and not by way of limitation.Depending on the need of the patient and the capability of theimplantable device, other arrangements and uses of these leads andelectrodes are possible.

The patient management system 100 may include a dynamically controlledstimulation circuit 113. The dynamically controlled stimulation circuit113 may determine therapy parameters dynamically according to patientpresent physiological or functional condition. Patient conditions suchas patient health status, HF progressions, remodeling or decompensation,heart rate, postures, posture transitions, physical activities,sleep/awake status, medication, hydration, diet, among other factors,may affect cardiac electrical and mechanical properties, andconsequently affect HF therapy efficacy. In an example, the dynamicallycontrolled stimulation circuit 113 may determine a stimulation site suchas between a LV-only pacing and a BiV pacing, or a stimulation mode suchas between a SSP and MSP, based on the sensor input. The dynamicallycontrolled stimulation circuit 113 may independently time AV conductioncharacteristic measurement using separate timers for a plurality ofheart rate ranges. The timers can be programmed with respective timerdurations, and can operate independently with respective reset andexpiration time. The multiple independently operated timers fordifferent heart rate ranges can be more effective in capturing patientAV conduction characteristics for the “rare heart rates.” Examples ofthe dynamically controlled stimulation circuit 113 are described below,such as with reference to FIG. 2.

The external system 120 may allow for programming of the IMB 110, andreceiving information from the IMD 110, via a communication link 103.The external system 120 may include a local external IMD programmer. Theexternal system 120 may include a remote patient management system thatmay monitor patient status or adjust one or more therapies such as froma remote location. The remote patient management system may evaluatecollected patient data and provide alert notifications, among otherpossible functions. In an example, the remote patient management systemmay include a centralized server acting as a central hub for collectedpatient data storage and analysis. The server can be configured as auni-, multi- or distributed computing and processing system. The remotepatient management system may additionally or alternatively include oneor more locally configured clients or remote clients securely connectedto the server. Examples of the clients may include personal desktops,notebook computers, mobile devices, or other computing devices. Systemusers, such as clinicians or other qualified medical specialists, mayuse the clients to securely access stored patient data assembled in thedatabase in the server.

The communication link 103 may include one or more of an inductivetelemetry link, a radio-frequency telemetry link, or a telecommunicationlink, such as an internet connection. The communication link 103 mayprovide for data transmission between the IMB 110 and the externalsystem 120. The transmitted data may include, for example, real-timephysiological data acquired by the IMD 110, physiological data acquiredby and stored in the IMD 110, therapy history data or data indicatingIMD operational status, programming instructions to the IMD 110 such asto configure the IMD 110 to perform one or more actions including, forexample, data acquisition, device self-diagnostic test, or therapydelivery.

The dynamically controlled stimulation circuit 113 may be implemented atthe external system 120 such as using data extracted from the IMB 110 ordata stored in a memory within the external system 120. Portions of thedynamically controlled stimulation circuit 113 may be distributedbetween the IMD 110 and the external system 120.

Portions of the IMB 110 or the external system 120 may be implementedusing hardware, software, or any combination of hardware and software.Portions of the IMB 110 or the external system 120 may be implementedusing an application-specific circuit that may be constructed orconfigured to perform one or more particular functions, or may beimplemented using a general-purpose circuit that may be programmed orotherwise configured to perform one or more particular functions. Such ageneral-purpose circuit may include a microprocessor or a portionthereof, a microcontroller or a portion thereof, or a programmable logiccircuit, or a portion thereof. For example, a “comparator” may include,among other things, an electronic circuit comparator that may beconstructed to perform the specific function of a comparison between twosignals or the comparator may be implemented as a portion of ageneral-purpose circuit that may be driven by a code instructing aportion of the general-purpose circuit to perform a comparison betweenthe two signals. While described with reference to the IMD 110, thepatient management system 100 could include a subcutaneous medicaldevice (e.g., subcutaneous ICD, subcutaneous diagnostic device),wearable medical devices (e.g., patch based sensing device), or otherexternal medical devices.

FIG. 2 illustrates an example of a dynamically controlled cardiacstimulation system 200. The dynamically controlled cardiac stimulationsystem 200 can be configured to provide diagnostic informationincluding, for example, changes of cardiac status at various patientphysiological or functional conditions, and recommend therapy parametersvalues such as timing, site, or mode of cardiac stimulation. Thedynamically controlled cardiac stimulation system 200 may include one ormore of a sensor circuit 210, a stimulation control circuit 230, amemory circuit 240, and a user interface 260. In some examples, thesystem 200 may additionally include a therapy circuit 270 configured todeliver a therapy such as cardiac stimulation. At least a portion of thecardiac monitoring system 200 may be implemented in an AMD, such as theIMD 110, or distributed between an AMD or and an external system such asthe external system 120.

The sensor circuit 210 may include a sense amplifier to sense a cardiacsignal. The cardiac signal may be sensed from different heart chambers,such as one or more of the RA, the RV, the left atrium (LA), or the LV.The cardiac signal may be sensed when the heart undergoes an intrinsicrhythm such as a sinus rhythm, or when the heart is stimulated inaccordance with a stimulation protocol, such as pacing at an atrium, aventricle, or other sites at a specified rate or timing sequence.Examples of the cardiac signal may include cardiac electrical signalssuch as ECGs sensed non-invasively from body surface, subcutaneous ECGssensed from subcutaneously placed electrodes, or intracardiac EGMssensed from electrodes on one or more of the leads 108A-C or the canhousing 112. By way of example and not limitation, atrial activation(denoted by AS) may be sensed using a sensing vector comprising one ofthe atrial electrodes 141 or 142, right ventricular activation (denotedby RVS) may be sensed using a sensing vector comprising one of the RVelectrodes 152-154, and left ventricular activation (denoted by LVS) maybe sensed using a sensing vector comprising one of the LV electrodes161-164.

Additionally or alternatively, the cardiac signals may include signalsindicative of cardiac mechanical activities or patient hemodynamicstatus. In an example, the cardiac signal may include a signal sensedfrom an accelerometer or a microphone configured to sense heart soundsin a patient. In an example, the cardiac signal may include a cardiac orthoracic impedance signal. The cardiac mechanical signals may includeblood pressure sensor signals or any other sensor signals indicative ofcardiac mechanical activities or hemodynamic status.

In some examples, the sensor circuit 210 may simultaneously orsequentially sense two or more cardiac signals from different sites of aheart chamber, such as multiple sites at the LV. The sensor circuit 210may sense LV EGMs from two or more LV sites using respective sensingvectors. An example of the LV sensing vector may include a bipolarsensing vector, such as between a pair of electrodes selected among161-164. Alternatively, the LV sensing vector may be between one of theelectrodes 161-164 and another electrode positioned on a differentchamber or on a different lead (such as one of electrodes 152-155 on theRV lead 108B, or electrodes 141 or 142 on the RA lead 108A). Anotherexample of the LV sensing vector may include a unipolar sensing vectorsuch as between one of the electrodes 161-164 and the can housing 112.

The sensor circuit 210 may process the sensed cardiac signal, includingamplification, digitization, filtering, or other signal conditioningoperations. From the processed cardiac signal, the sensor circuit 210may detect signal features, or perform measurements that indicatepatient cardiac condition or therapy efficacy, or a complicationintroduced by the stimulation. Examples of the signal features mayinclude temporal or morphological features indicative of intrinsiccardiac activity such as a P wave, Q wave, R wave, QRS complex, or Twave that may be detected from a surface ECG, a subcutaneous ECG, or anintracardiac EGM, timing and intensity of evoked cardiac activity suchas evoked electrical or mechanical activation in response to anelectrostimulation of the heart. Examples of the timing measurement mayinclude a time delay between cardiac activations sensed at differentheart chambers (e.g., PRI or AVI between an atrium and a ventricle, orRV to LV sensed interval), or between different pacing sites (e.g.,sensing delay among various LV sites).

The sensor circuit 210 may additionally receive information aboutpatient long-term or short-term physiological or functional conditions.Changes in long-term or short-term patient conditions may affect cardiacelectrical and mechanical properties and patient hemodynamic responses.As a result, a therapy may be less effective if not timely and properlyadjusted to accommodate the changing patient condition. Physiologicalsignals, such as cardiac, pulmonary, neural, or biochemical signals, maybe received at the sensor circuit 210. Examples of the physiologicalsignals may include ECG, intracardiac EGM, a heart rate signal, a heartrate variability signal, a cardiovascular pressure signal, a heartsounds signal, a respiratory signal, a thoracic impedance signal, arespiratory sounds signal, or blood chemistry measurements or expressionlevels of one or more biomarkers. Examples of the functional signals mayinclude patient posture, gait, balance, or physical activity signals,among others. The sensor circuit may sense the functional signals usinga motion sensor, such as an accelerometer, gyroscope (which may be aone-, two-, or three-axis gyroscope), magnetometer (e.g., a compass),inclinometers, goniometers, altimeters, electromagnetic tracking system(ETS), or a global positioning system (GPS) sensor, among others. Inanother example, the functional signal may include information aboutsleep state signal, such as sleep or awake state, frequency or durationof sleep position switch, sleep incline, or other indicators of sleepquality. In another example, the functional signal may includeinformation on food or drink intake (e.g., swallow), coughing oraspiration detection. In some examples, information about patientphysiological or functional conditions may be stored in a storagedevice, such as an electronic medical record (EMR) system, and thesensor circuit 210 can be configured to receive the patient conditionfrom the storage device in response to a user input or triggered by aspecific event.

In some examples, the sensor circuit 210 may receive information aboutpatient medical history, medication intake, hospitalization, surgicalprocedures, cardiac remodeling, worsening heart failure events such asheart failure decompensation, or HF comorbidities. In some examples, thesensor circuit 210 may receive device implant information, such asposition of an implantable lead. For example, an LV lead 108C may beimplanted at free wall, anterior, lateral, or posterior, among otherpossible LV positions. LV lead location may affect the therapy efficacy,and be used for determining the stimulation site, mode, and timingparameter. In some examples, the sensor circuit 210 may additionallyinclude patient echocardiography-derived measurements, such as ejectionfraction, cardiac contractility, cardiac timing, or aortic velocity,among other hemodynamic parameters or other clinical diagnostics.

The stimulation control circuit 230 may generate diagnostics aboutchanges of cardiac status at a particular patient physiological orfunctional condition as received from the sensor circuit 210, andrecommend therapy parameter values including, for example, timing, site,or mode of cardiac stimulation. The stimulation control circuit 230 maybe implemented as a part of a microprocessor circuit, which may be adedicated processor such as a digital signal processor, applicationspecific integrated circuit (ASIC), microprocessor, or other type ofprocessor for processing information including physical activityinformation. Alternatively, the microprocessor circuit may be ageneral-purpose processor that may receive and execute a set ofinstructions of performing the functions, methods, or techniquesdescribed herein.

The stimulation control circuit 230 may include circuit sets comprisingone or more other circuits or sub-circuits, such as one or more of aparameter sampling control circuit 235, a stimulation site selectorcircuit 231, a stimulation mode selector 232, and a stimulation timingadjuster circuit 233. These circuits may, alone or in combination,perform the functions, methods, or techniques described herein. In anexample, hardware of the circuit set may be immutably designed to carryout a specific operation (e.g., hardwired). In an example, the hardwareof the circuit set may include variably connected physical components(e.g., execution units, transistors, simple circuits, etc.) including acomputer readable medium physically modified (e.g., magnetically,electrically, moveable placement of invariant massed particles, etc.) toencode instructions of the specific operation. In connecting thephysical components, the underlying electrical properties of a hardwareconstituent are changed, for example, from an insulator to a conductoror vice versa. The instructions enable embedded hardware (e.g., theexecution units or a loading mechanism) to create members of the circuitset in hardware via the variable connections to carry out portions ofthe specific operation when in operation. Accordingly, the computerreadable medium is communicatively coupled to the other components ofthe circuit set member when the device is operating. In an example, anyof the physical components may be used in more than one member of morethan one circuit set. For example, under operation, execution units maybe used in a first circuit of a first circuit set at one point in timeand reused by a second circuit in the first circuit set, or by a thirdcircuit in a second circuit set at a different time.

The stimulation site selector circuit 231 can be configured to determinea heart chamber for pacing according to the received patient condition.In an example, the stimulation site selector circuit 231 may selectbetween an LV-only pacing and a BiV pacing. The BiV pacing refers tostimulation of both the LV and RV simultaneously or sequentially with aspecified time offset. In some patients, the BiV pacing may offer bettercardiac synchrony and cardiac contractility than the LV-only pacingconfigured for only stimulating the LV. However, a change in patientphysiological or functional condition (e.g., a heart rate increase, or aposture transition from supine to standing) may alter AV condition,ventricular contractility, or other cardiac properties. Pacing chambermay need to be switched, among other therapy adjustments, to maintainadequate therapy efficacy. The stimulation site selector circuit 231 mayinitiate stimulation site assessment in response to a change of patientcondition, and determine between an LV-only pacing and BiV pacing basedon a heart rate increase, and an indicator of AV conduction abnormality,such as an extension of PRI or AVI or increased irregularity of the PRIor AVI. An example of determining stimulation site between LV-onlypacing and BiV pacing in accordance with changes in patient conditionsis disclosed in the commonly assigned U.S. patent application Ser. No.16/007,094 by Ternes et al., entitled “SYSTEMS AND METHODS FOR DYNAMICCONTROL OF HEART FAILURE THERAPY,” which is hereby incorporated byreference in its entirety.

The stimulation mode selector circuit 232 can be configured to determinebetween a single site pacing (SSP) and a multisite pacing (MSP)according to the received patient condition. The MSP may be delivered attwo or more sites inside, or on an epicardial surface of, one or moreheart chambers or tissues surrounding any of the chambers. During MSP,pulse trains may be delivered at the two or more cardiac sitessimultaneously, or sequentially with an intra-ventricular delay lessthan a sensed or paced time interval value of the cardiac cycle. In anexample, the stimulation mode selector circuit 232 may initiatestimulation mode assessment in response to a change of patientcondition, and determine between SSP pacing and a MSP pacing at two ormore LV sites using inter-ventricular intervals measured from RV site tovarious candidate LV sites, such as those corresponding to the LVelectrodes 161-164. The inter-ventricular intervals represent degrees ofdyssynchrony between RV and various LV sites. The stimulation modeselector circuit 232 may scan through a plurality of candidate LVelectrodes to identify those LV sites with the correspondinginter-ventricular intervals satisfying a specified condition, such as apatient condition-indicated threshold value, and select SSP or MSP basedon the candidate electrodes identification. Commonly assigned U.S.patent application Ser. No. 16/007,094 by Ternes et al., entitled“SYSTEMS AND METHODS FOR DYNAMIC CONTROL OF HEART FAILURE THERAPY”discloses a method of determining stimulation mode between SSP and MSPin accordance with changes in patient conditions, the disclosure ofwhich is hereby incorporated by reference in its entirety.

The stimulation timing adjuster circuit 233 can be configured todetermine or update a stimulation timing parameter using patientphysiological or functional information, such as measurements of AVconduction characteristic. The stimulation timing parameter may bedetermined or updated at a particular time, or at a particular periodicupdate rate. The stimulation timing parameter defines the timingsequence for delivering cardiac stimulation (e.g., ventricular pacing).Such timing sequence can be important to ensure therapy efficacy andpatient hemodynamic outcome. Examples of the timing parameter mayinclude AVD, VVD, or ILVD. In an example, the stimulation timingadjuster circuit 233 may determine or update AVD using patient intrinsicAVI under the received patient condition. The AVI may be measureddirectly from the sensed cardiac signal under a specific patientcondition. Alternatively, the AVI may be estimated dynamically duringpacing. Commonly assigned U.S. patent application Ser. No. 16/007,094 byTernes et al., entitled “SYSTEMS AND METHODS FOR DYNAMIC CONTROL OFHEART FAILURE THERAPY” discloses a method of AVI estimation duringpacing using a combination of the AVD that leads to pseudo-fusion andthe stored offset, the description of which is hereby incorporated byreference in its entirety.

In some examples, the stimulation timing adjuster circuit 233 maydetermine or update a stimulation timing parameter (e.g., AVD) using aweighted combination of (1) a historical stimulation timing parametervalue and (2) the determined value of the AV conduction characteristic,each scaled by respective weight factors. In an example, an AVD may beupdated recursively using intrinsic AVI values as follows:AVD(n)=a*AVD(n−1)+b*AVI(n)  (1)where AVD (n) denotes a newly updated AVD value, AVD(n−1) denotes ahistorical AVD value prior to the update, and AVI(n) denotes a presentlymeasured or estimated intrinsic AVI value. In an example, thestimulation timing adjuster circuit 233 can adjust one or more of theweight factors “a” or “b” using information of physical activity of thepatient. When patient physical activity increases, the intrinsic AVI maychange more substantially. Accordingly, AVD may be adjusted to addressthe change in AVI. In an example, in response to elevated physicalactivity, the stimulation timing adjuster circuit 233 can decrease theweight factor “a”, and/or increase the weight factor “b” such that theAVD is more sensitive to the present AVI.

In an example, the stimulation timing adjuster circuit 233 may determineor update AVD using a combination of an AVI measured at the rightventricle (AV_(R)) and an AVI measured at the left ventricle (AV_(L)).The AV_(R) represents an interval between an atrial sensed (AS) oratrial paced (AP) activation to a sensed RV activation (RVS). The AV_(L)represents an interval between an AS or an AP activation to a sensed LVactivation (LVS). Commonly assigned U.S. patent application Ser. No.16/007,094 by Ternes et al., entitled “SYSTEMS AND METHODS FOR DYNAMICCONTROL OF HEART FAILURE THERAPY” discusses a method of determining AVDusing a linear weighted combination of AV_(R) and AV_(L), the disclosureof which is hereby incorporated by reference in its entirety.

The parameter sampling control circuit 235 can be configured toindependently sample the AV conduction characteristic for a plurality ofheart rate ranges. In an embodiment, the parameter sampling controlcircuit 235 may include separate timers respectively for the pluralityof heart rate ranges. The timers can be programmed with respective timerdurations, and operate independently with respective reset andexpiration time. The timers can enable or disable measurement of AVconduction characteristic for the corresponding heart rate ranges basedon the states of the respective timer (e.g., whether or not the timerhas timed out or expired). For a heart rate (intrinsic heart rate, orheart rate during atrial pacing) detected in a heart rate range, the AVconduction characteristic can be sampled only when the timer,corresponding to the particular heart rate range, times out. Forexample, when a first timer blocks sampling AV conduction characteristicfor a detected heart rate falling in one heart rate range, a differentsecond timer may still enable sampling AV conduction characteristic fora detected heart rate falling in a different heart rate range, providedthe second timer has timed out. In some examples, the parameter samplingcontrol circuit 235 may include a global timer having a duration, andthe separate timers included in the parameter sampling control circuit235 may be triggered to enable or disable measurement of AV conductioncharacteristic in response to an expiration of the global timer.Compared to conventional periodic sampling at a fixed interval or rateirrespective of heart rates, the heart rate-indicated timers can allowthe parameter sampling control circuit 235 to more reliably capturepatient AV conduction characteristics for the “rare heart rates,” whileat the same time substantially reduce the repetitive sampling of AVconduction characteristics for the “frequent heart rates.” Examples oftiming control for sampling AV conduction characteristics usingheart-rate indicated timers are discussed below, such as with referenceto FIGS. 3-4.

The memory circuit 240 can be configured to store a set of stimulationparameters, such as AVDs. The stimulation timing parameters maycorrespond to each of a plurality of heart rates or heart rate ranges.In some examples, the stimulation timing parameters may furthercorrespond to other patient conditions such as atrial sensed (AS) eventsor atrial paced (AP) events, different postures, or different time of aday. In some examples, the memory circuit 240 may store a stimulationparameter table including stimulation timing parameter values and thecorresponding plurality of heart rates or heart rate ranges, optionallywith one or more other patient conditions (e.g., postures), orinformation of time of a day, as illustrated in FIG. 5A-5C below.

The stimulation timing adjuster circuit 233, coupled to the memorycircuit 240, may search for the received patient condition from thestimulation parameter table, and identify a recommended AVDcorresponding to that patient condition. The stimulation timing adjustercircuit 233 may perform dynamic AVD adjustment by switching to theapplicable table entry whenever the patient is in that condition. In anexample, the AVD may be adjusted on a beat-by-beat basis, orperiodically at specified time.

The user interface 260 may include an input device that enables a systemuser to program the parameters used for electrostimulation or forsensing the cardiac signals. Examples of the input device may include akeyboard, on-screen keyboard, mouse, trackball, touchpad, touch-screen,or other pointing or navigating devices. The input device may enable thesystem user to activate automated programming of HF therapy, such asautomated determination of stimulation site, stimulation mode, andstimulation timing parameters under a specific patient condition. Theinput device may also enable the system user to confirm, reject, orotherwise modify the automatically determined therapy programming.

The user interface 260 may include a display for display therapyprogramming such as automatically determined stimulation site,stimulation mode, and stimulation timing parameters. The output unit 230may include a printing device for producing a hardcopy of theinformation. The information may be presented in a table, a chart, atrend, a diagram, or any other types of textual, tabular, or graphicalpresentation formats. Additional information for displaying may includecardiac signals, signal features or measurements (e.g., PRI or AVI)derived from the sensed cardiac signal, information of patientphysiological or functional conditions received from the sensor circuit210, or device status information such as lead impedance and integrity,battery status such as remaining lifetime of the battery, or cardiacstimulation threshold, or complications associated with stimulation atone or more cardiac sites, among others.

The therapy circuit 270 can be configured to generate therapy accordingto the parameter values generated and recommended by the stimulationcontrol circuit 230. The therapy may include electrostimulationdelivered to the pacing sites via one or more of the leads 108A-C andthe respectively attached electrodes. The therapy circuit 270 can beconfigured to deliver LV-only pacing, or BiV pacing. Additionally oralternatively, the therapy circuit 270 can be configured to generate SSPfor stimulating one cardiac site, or a MSP for stimulating two or moresites of the heart within the same cardiac cycle. In an example, the MSPmay be delivered within the LV. The LV MSP may have a unipolar pacingconfiguration where only one electrode (e.g., a cathode) is a LVelectrode and the other electrode (e.g., an anode) is the IMD canhousing 112. In another example, a true bipolar configuration may beused, where both the cathode and anode are LV electrodes. In yet anotherexample, an extended bipolar configuration may be used, where oneelectrode (e.g., a cathode) is a LV electrode and the other electrode(e.g., an anode) is a RA electrode such as one of the electrodes 141 or142, or a RV electrode such as one of the electrodes 152-155. In anotherexample, a tripolar configuration may be used, which may include two LVelectrodes used jointly as a cathode, or two electrodes such as selectedfrom the RA and RV electrodes used jointly as an anode. In an example,one or more LV electrodes may be distributed in one or more LV leads,catheters, or untethered pacing units.

In some examples, the therapy circuit 270 may initiate or adjustelectrostimulation at non-cardiac tissues such as nerve tissues, orother therapy types, such as a cardioversion therapy, a defibrillationtherapy, or drug therapy including delivering drug to a tissue or organ.In some examples, the therapy circuit 270 may modify an existingtherapy, such as adjust a stimulation parameter or drug dosage.

FIG. 3 is a block diagram illustrating an example of a heartrate-indicated AVI sampling control circuit 300 configured to sample AVconduction characteristics for heart rates detected in a plurality ofheart rate ranges. In this document, the sampling of a physiologicparameter refers to measuring the physiologic parameter according to aschedule, such as at a particular time or a periodic sampling rate(e.g., performing a measurement once every 5 minutes). The heartrate-indicated AVI sampling circuit 300, which is an embodiment of theparameter sampling control circuit 235 of the system 200 shown in FIG.2, can include a HR zone detector 310, a timing control module 320, andAVI sampler modules 330. The HR zone detector 310 can monitor patientheart rate continuously or intermittently, and detect a heart rate inone of a plurality of heart rate ranges HR range 1 (HR_1) through HRrange N (HR_N). The heart rate can be an intrinsic heart rate in theabsence of atrial pacing. Alternatively, the heart rate can be detectedduring atrial pacing. Such atrial-paced heart rate is substantiallyequivalent to atrial pacing rate. The heart rate ranges can benon-overlapping to each other. By way of example and not limitation,HR_1 is <60 bpm, HR_2 is 60-70 bpm, HR_3 is 70-90 bpm, HR_4 is 90-120bpm, etc.

The timing control module 320 can include a plurality of timers, Timer_1through Timer_N, corresponding to the HR ranges HR_1 through HR_N. Thesetimers can have respective programmable durations (e.g., Dur_1 throughDur_3, for Timer_1 through Timer_N, respectively), and are configured toindependently time the measurement of AV conduction characteristic, suchas enabling or disabling the measurement of intrinsic AVI, for thecorresponding heart rate ranges. Once an AVI value is measured in thecorresponding HR range, the corresponding timer can be reset, and isconfigured to expire after a timer duration since the reset time. Thetimers can have different reset and expiration time. As a result, when afirst timer (e.g., Timer_1) blocks sampling an AVI value for a detectedheart rate falling in one heart rate range (HR_1) because the firsttimer has not timed out, a second timer (e.g., Timer_2) may still enablesampling an AVI value for a detected heart rate falling in a differentheart rate range (e.g., HR_2), provided the second timer has timed out.

The AVI sample modules 330 can include a plurality of sampler modules,Sampler_1 through Sampler_N, corresponding to the Timer_1 throughTimer_N. The sampler modules are each configured to sample AV conductioncharacteristic (e.g., measuring AVI values) during a particular timeperiod or a time window for the heart rates detected in thecorresponding hear rate range, while at other times can block AVIsampling for the heart rates detected in the corresponding heart raterange. In an example, when a heart rate is sensed in a heart rate rangeHR_k, the corresponding sampler module, Sampler_k, can sample AVI onlywhen the corresponding timer, Timer_k, times out. That is, Sampler_kfollows a sampling control mechanism to enable AVI measurement only when(1) a heart rate is detected in the range HR_k; and (2) the Timer_k isin a timeout or expired state. Examples of independent timing control ofsampling AVI using multiple timers for a plurality of heart rate rangesare discussed below with reference to FIG. 4. Such a timing controlmechanism can be more effective in capturing patient AV conductioncharacteristics for the “rare heart rates,” and at the same time cansubstantially reduce the repetitive sampling of AV conductioncharacteristics for the “frequent heart rates.”

Because the AVI sampler modules 330 can enable AVI sampling and AVDupdate only when the corresponding heart rate-indicated timer has timedout after a programmed timer duration has elapsed, the timer duration,among other things, can therefore determine a rate of periodic AVIsampling and AVD update. In an example, the timer durations fordifferent heart rate ranges can be identical. For example,Dur1=Dur2=Dur3=10 minutes. Alternatively, at least some timer durationsare distinct from each other. In an example, a higher heart rate rangecan be associated with a shorter timer duration for the correspondingtimer, thus more frequent AVI sampling, than a lower heart rate range.For example, a timer corresponding to a heart rate range of 100-120 bpmcan have a shorter duration than another timer corresponding to a heartrate range of 70-80 bpm. Because HF patients are more likely to developconduction abnormalities at higher heart rate and thus changes in AVconduction characteristic, a shorter timer duration (or equivalentlymore frequent evaluation of AVI) can ensure timely capture the changesin AVI and adjust of therapy accordingly (e.g., via an updated AVD).

In some examples, the timer duration can be determined based on aprevalence indicator of the heart rates in each HR range. The prevalenceindicator represents an occurrence rate of the heart rates falling in aHR range. For a HR range with more prevalent heart rates, a longer timerduration may be programmed to the corresponding timer. Accordingly, fora heart rate range with more prevalently detected heart rates (or the“frequent heart rates”), a longer timer duration can reduce AVI samplingand AVD update. Due to their reduced cardiac functional capacity, heartfailure patients generally have a narrower intrinsic heart rate rangethan healthy subjects. For example, heart rates are more prevalentlyobserved in a hear rate range of 50-80 bpm than a higher rate range of100-120 bpm. A longer timer duration for a heart rate range of “frequentheart rates” and a shorter timer duration for a heart rate range of“rare heart rates” can be advantageous, as the system resources can besaved for sampling the AVI and updating the AVD for the less prevalent,“rare heart rates.” It may also help reduce repetitive sampling of AVIfor the “frequent heart rates” at least because the AVD less likelyneeds to be updated for the frequent heart rates.

In some examples, at least some timer durations can be updated. Theupdate can occur periodically at a specified time or periodicity, or inresponse to a trigger event. In some examples, the timing or frequencyfor updating the timer durations can be automatically determined.

The timing control module 320 may additionally include a global blankingcircuit 322 configured to generate a global blanking period (T_(B))immediately following an AVI measurement carried out by any sampler inthe AVI sampler modules 330. In an example, the global blanking periodT_(B) can be approximately 1 minute. During the global blanking period,AVI measurement in all HR ranges can be disabled, regardless of theheart rate or the state of any timer (whether or not timed out). Alsoimmediately following the AVI measurement such as by the Sampler_k, thecorresponding timer Timer_k can be reset to its duration Dur_k. Timer_kthen counts down as its duration Dur_k elapses, and subsequent AVImeasurement is disabled for any heart rate falling in the range HR_k,until the Timer_k expires. In contrast to the global blanking periodT_(B) that affects all samplers, a reset of a particular timer (e.g.,Timer_k) has a blanking effect only on the corresponding sampler (e.g.,Sampler_k), and does not block other samplers from sampling the AVI.

In some examples, the heart rate-indicated AVI sampling circuit 300 mayinclude a global timer having a duration. The samplers Sampler_1 throughSampler_N may be triggered to enable or disable measurement of AVconduction characteristic in response to an expiration of the globaltimer. In an example, the global timer can operate in a similar fashionas one of the Timers_1 through Timer_N.

FIG. 4 is a diagram illustrating, by way of example and not limitation,events during sampling of AVI values and updating AVD for respectiveheart rate ranges. For the purpose of illustration, threenon-overlapping HR ranges are shown: HR_1 of 60-70 bpm, HR_2 of 80-90bpm, and HR_3 of 100-120 bpm. Corresponding to the heart rate rangesHR_1 through HR_3, AVI samplers Sampler_1 through Sampler_3 canindependently sample AVI values during a particular time period or atime window. Each timer has a pre-determined timer duration, such asDur1 for HR_1, Dur2 for HR_2, and Dur3 for HR_3. In an example, alltimer durations are identical. Alternatively, the timer duration can bedifferent across different heart ranges. In an example, a timer for ahigher heart rate range has a shorter duration (thus more frequent AVIreevaluation and AVD update) than a timer for a lower heart rate range.Each timer can be reset upon sampling an AVI value in the correspondingHR range, and configured to expire after the timer duration has elapsed.

Heart rates can be continuously or intermittently monitored, and a heartrate signal 401 can be generated using the parameter sampling controlcircuit 300. The heart rates can be intrinsic heart rates in the absenceof atrial pacing. Alternatively, the heart rates can be detected duringatrial pacing. Such atrial-paced heart rates are substantiallyequivalent to atrial pacing rates. Initially, all timers, includingTimer_1 through Timer_3, are timeout or expired. At time T0, a heartrate of 65 bpm is detected in HR_1. Because Timer_1 is in a timeoutstate, Sampler_1 is triggered to open an window 411 to sample anintrinsic AVI value AVI₁₁, during which ventricular pacing (e.g., CRTtherapy) can be temporarily suspended. The measured AVI₁₁ can then beused to update AVD for HR_1, such as using Equation (1). The windowopened for intrinsic AVI measurement may be one cardiac cycle.Alternatively, the window may open to sample multiple AVI values in twoor more cardiac cycles, either continuously or intermittently.

Immediately following the AVI measurement, a global blanking period 412can be generated and applied. During the global blanking period 412 witha duration of T_(B), AVI measurement in all HR ranges, including HR_1,HR_2, and HR_3, are disabled. In an example, T_(B) is approximately 1minute. Also immediately following the AVI measurement at 411, Timer_1can be reset. This disables Sampler_1 from sampling AVI for any heartrates detected in HR_1. However, resetting of Timer_1 has no impact onother samplers to sample AVI in the corresponding heart rate ranges,provided the heart rate and timer state conditions are met in thoseheart rate ranges.

At T1, HR of 68 bpm is sensed in HR_1. Since it occurs before Timer_1gets expired, no AVI window can be opened, and no AVD update is carriedout for HR_1. At T2, HR of 85 bpm is sensed in HR_2. The correspondingTimer_2 is in an timeout state, so Sampler_2 is triggered to open awindow 421 to measure an intrinsic AVI value (AVI₂₁), while theventricular pacing is temporarily suspended. The AVI₂₁ can then be usedto update AVD for HR_2. Immediately following the AVI measurement at421, a global blanking period 422 can be applied to block AVImeasurement in any HR ranges during T_(B), and Timer_1 is reset to blockAVI measurement only in HR_2 during Dur2.

At T3, HR of 102 bpm is sensed in HR_3. Although Timer_3 is in a timeoutstate, the detected HR occurs falls within the global blanking period422. Therefore, no AVI window can be opened, and no AVD update wouldoccur for HR_3.

At T4, HR of 105 bpm is sensed in HR_3, and it does not fall within anyglobal blanking period. Because the corresponding Timer_3 is in atimeout state, the Sampler_3 is triggered to open a window 431 tomeasure an intrinsic AVI value (AVI₃₁), during while the ventricularpacing is temporarily suspended. The AVI₃₁ can then be used to updateAVD for HR_3. Immediately following the AVI measurement at 431, a globalblanking period 432 is applied to block AVI measurement in any HR rangesduring T_(B), and Timer_3 is reset to block AVI measurement only in HR_3during Dur3.

At T5, HR of 83 bpm is sensed in HR_2. However, Timer_2 has not yetexpired at the detection of this heart rate. Therefore, no AVI windowcan be opened, and no AVD update would occur for HR_2.

At T6, HR of 61 bpm is sensed in HR_1. At this moment, Timer_1 hasexpired. Therefore, the Sampler_1 is triggered to open a window 413 tomeasure an intrinsic AVI value (AVI₁₂). The AVI₁₂ can then be used toupdate AVD for HR_1. Immediately following the AVI measurement at 413, aglobal blanking period 414 can be generated to block AVI measurement inany HR ranges during T_(B), and Timer_1 is reset to block AVImeasurement only in HR_1 for a duration Dur1.

At T7, HR of 87 bpm is sensed in HR_2. At this moment, Timer_2 hasexpired. Therefore, the Sampler_2 is triggered to open a window 423 tomeasure an intrinsic AVI value (AVI₂₂) while the ventricular pacing istemporarily suspended. The AVI₂₂ can then be used to update AVD forHR_2. Immediately following the AVI measurement at 423, a globalblanking period 424 can be generated to block AVI measurement in any HRranges during T_(B), and Timer_2 is reset to block AVI measurement onlyin HR_2 for a duration Dur2.

As illustrated in FIG. 4, with the multiple, heart rate-indicated timersTimer_1 through Timer_3 and the sampling control mechanism discussedherein, AVI values corresponding to “rare heart rates” in HR ranges HR_2or HR_3 can be reliably sampled, while repetitive sampling of AVI valuescorresponding to “frequent heart rates” (e.g., in HR_1) can beeffectively avoided or reduced.

FIGS. 5A-5C are diagrams illustrating patient condition-indicatedstimulation parameter values, which can be stored in a memory fordynamic cardiac pacing. The stimulation parameters can be stored in atable, such as table 510, 520, or 530, that includes recommendedstimulation timing values along with one or more corresponding patientconditions. Each table entry may include a recommended AVD value under acorresponding patient condition. By way of example and not limitation,FIG. 5A illustrates a stimulation parameter table 510 that includesstimulation timing values, such as AVD values, with corresponding heartrate ranges (HR), and atrial activation mode as either atrial sensed(AS) event or atrial paced (AP) events. The AVD for an AS event isreferred to a sensed AVD, and the AVD for an AP event is referred to apaced AVD. FIG. 5B illustrates a stimulation parameter table 520, whichis a variant of the Table 510 augmented by patient postures. By way ofexample, the postures included in the Table 520 include supine, sitting,or standing postures. FIG. 5C illustrates a stimulation parameter table530, which is another variant of the Table 510 augmented by informationof time of a day, such as a daytime or a nighttime. Alternatively, thetime of a day may include a number of time periods during a day within a24-hour period. In various examples, table 510, 520, or 530 may beaugmented to include other patient conditions, such as activity (walkingor running,) sleeping, diet, hydration, medication intake, heart rate,heart rate variability, arrhythmic events (e.g., atrial fibrillation,ventricular tachycardia, premature ventricular contractions, postarrhythmia). Various combination or permutations of patient conditionscan be implemented in a stimulation parameter table similar to the table510-530, which is within the scope of the present document. Thesepatient conditions, individually or in combination, may affect cardiactissue properties and patient hemodynamics. As a result, a therapyprogrammed under one condition may not be equally effective under adifferent condition. Different AVD values may be recommended atdifferent patient conditions to achieve desirable therapy efficacy andpatient outcome.

In various examples, at least some entries of a stimulation parametertable may additionally or alternatively include recommended values ofstimulation timing parameters other than AVD. In an example, the tableentry may include a recommended RV-LV delay (VVD) under correspondingpatient conditions of heart rate, posture, and atrial activation mode.The VVD represents an offset between an LV pacing pulse and a RV pacingpulse within a cardiac cycle for BiV pacing or CRT therapy such asselected by a system user or determined by the stimulation controlcircuit 230. In some examples, the VVD can be set to zero such that LVpacing and RV pacing are simultaneously delivered. In another example,at least some table entries may include a recommended intra-LV timeoffset (ILVD). The ILVD represents an offset between LV pacing pulsesseparately delivered at different LV sites within a cardiac cycle when aLV MSP is selected by a system user or determined by the stimulationcontrol circuit 230. The LV MSP may be delivered via two or more of theLV electrodes 161-164 as illustrated in FIG. 1.

In various examples, the stimulation parameter table may be augmented toinclude information in addition to the stimulating timing parameters. Inan example, at least some entries of Tables 510-530 may additionally oralternatively include information about stimulation site such as anindication of LV-only pacing or a BiV pacing, or information aboutstimulation mode such as an indication of SSP or MSP. The augmentedtable thus provides comprehensive therapy recommendations on stimulationsite, mode, and timing values at various patient conditions. In anexample, the entries of the augmented table may be constructed as aclass structure in the memory circuit 250 that contains values of one ormore of the stimulation site, mode, and timing parameters. For example,one table entry may include (AVD, LV-only pacing), and another tableentry may include (AVD, BiV pacing, VVD, MSP, ILVD). In an example, oneelement in a table entry (e.g., AVD value, BiV pacing, or MSP) may beapplied to a number of table entries that share a common condition. Forexample, if BiV pacing is recommended for a condition defined by sittingposture, AS, and HR great than 100 bpm, then BiV pacing may berecommended for all conditions as long as containing a “sitting”posture, regardless of heart rate ranges, or atrial activation mode (ASor AP). In another example, if MSP is recommended for a conditiondefined by standing posture, AS, and HR within 70-80 bpm, then MSP maybe recommended for all conditions as long as containing a “standing”posture, regardless of heart rate ranges, or atrial activation mode.

In some examples, multiple tables of stimulation timing parameter valuesmay be constructed and stored in the memory circuit 250, such as an AVDtable containing only AVD values under various patient conditions, a VVDtable containing only VVD values under various patient conditions, or anILVD table containing only ILVD values under various patient conditions.The tables may include different patient physiological or functionalconditions. In an example, the stimulation control circuit 230 may referto the VVD table to determine an optimal VVD value under a specificpatient condition when a BiV pacing is selected. In another example, thestimulation control circuit 230 may refer to the ILVD table to determinean optimal ILVD value under a specific patient condition when MSP modeis selected. In another example, the stimulation control circuit 230 mayrefer to AVD table to determine an optimal AVD under a specific patientcondition irrespective of pacing site or pacing mode.

FIG. 6 is a flow chart illustrating a method 600 for updating astimulation parameter and delivering cardiac stimulation using theupdated stimulation parameter. The stimulation parameter, such as astimulation timing parameter, may be updated using intrinsic AVconduction characteristics (e.g., AVI) that are sampled by a pluralityof timers corresponding to a plurality of heart rate ranges. The method600 can be implemented in and executed by an implant device, such as theIMD 110, or the dynamically controlled cardiac stimulation system 200.

The method 600 commences at 610, where patient heart rates can bemonitored continuously or intermittently, such as using a cardiacelectrical or mechanical signal received by the sensor circuit 210. Theheart rates can be intrinsic heart rates in the absence of atrialpacing. Alternatively, the heart rates can be detected during atrialpacing. Such atrial-paced heart rates are substantially equivalent toatrial pacing rates. A heart rate can be detected in a target heart rage(e.g., HR_k) among a plurality of heart rate ranges HR_1 through HR_N.The plurality of heart ranges can be non-overlapping to each other.

A set of timers Timer_1 through Timer_N can be used for timing controlof sampling AV conduction characteristic. The sampling of an AVconduction characteristic refers to measuring the AV conductioncharacteristic (e.g., AVI) according to a schedule, such as at aparticular time or a periodic sampling rate (e.g., performing ameasurement once every 5 minutes). The set of timers correspond to theplurality of heart rate ranges, as illustrated in FIG. 3 in anon-limiting example. The timers can be programmed with respective timerdurations, and operate independently with respective reset andexpiration time. The timers can enable or disable measurement of AVconduction characteristic for the corresponding heart rate ranges basedon the states of the respective timer (e.g., whether or not the timerhas timed out or expired).

At 620, when the sensed heart rate is detected in the target heart raterange HR_k, if the corresponding timer Timer_k is in a timeout orexpired state, then an AV conduction characteristic (e.g., AVI) valuecan be sampled. Upon completion of the sampling process, at 630 theTimer_k, corresponding to the target heart range HR_k, can be reset toits duration Dur_k. Timer_k then counts down as its duration Dur_kelapses, and subsequent AVI measurement is disabled for any sensed heartrate falling in the range HR_k, until the Timer_k expires.

In some examples, an AVI measurement carried out by any sampler maytrigger a global blanking period (T_(B)). In an example, the globalblanking period T_(B) can be approximately 1 minute. During the globalblanking period, AVI measurement in all HR ranges can be disabled,regardless of the sensed heart rate or the state of any timer (whetheror not timed out).

At 640, at least a portion of a set of stimulation parameters stored ina memory and corresponding to the target heart rate range HR_k can bedynamically updated using the measured AV conduction characteristic. Astimulation timing parameter may be updated using patient physiologicalor functional information, such as measurements of AV conductioncharacteristic. The stimulation timing parameter defines the timingsequence for delivering cardiac stimulation, and can be important toensure therapy efficacy and patient hemodynamic response. The timingparameter may include AVD, VVD, or ILVD. In an example, the AVD can beupdated using patient intrinsic AVI measured at 620. In an example, theAVD can be updated recursively using a weighted combination of (1) ahistorical stimulation timing parameter value and (2) the determinedvalue of the AV conduction characteristic, each scaled by respectiveweight factors, such as according to Equation (1) above. In an example,one or more of the weight factors may be determined using information ofphysical activity of the patient. For example, in response to elevatedphysical activity, the weight factor for historical AVD value to can bereduced and/or the weight factor for present AVI measurement can beincreased, such that the updated AVD is more sensitive to the presentAVI. In another example, the AVD may be updated using a combination ofan AVI measured at the right ventricle (AV_(R)) and an AVI measured atthe left ventricle (AV_(L)).

The updated portion of the set of stimulation parameters can be storedin the memory. The stimulation timing parameters may correspond to eachof a plurality of heart rates or heart rate ranges. In some examples,the stimulation timing parameters may further correspond to otherpatient conditions such as atrial sensed (AS) events or atrial paced(AP) events, different postures, or different time of a day. In someexamples, a stimulation parameter table may be created and stored in thememory. The table can include stimulation timing parameter values andthe corresponding plurality of heart rates or heart rate ranges,optionally with one or more other patient conditions (e.g., postures),or information of time of a day, as illustrated in FIG. 5A-5C.

At 650, a stimulation parameter can be selected from the set of thestimulation parameters stored in the memory, including the updatedstimulating timing parameters, for use during cardiac stimulation. For areceived patient condition (e.g., a heart rate sensed from the patient,an AS or AP event, a posture, or a time of a day), a recommendedstimulation parameter (e.g., AVD) corresponding to that patientcondition may be identified. Cardiac stimulation (e.g., CRT) may bedelivered using the selected stimulation parameter. In various examples,a heart chamber (e.g., LV-only pacing, or BiV pacing of both left andright ventricles), or a pacing mode for pacing a heart chamber (e.g., asingle site pacing (SSP), or a multisite pacing (MSP), of a leftventricle), may be determined based on patient condition, as discussedabove with reference to FIG. 2.

FIG. 7 illustrates a block diagram of an example machine 700 upon whichany one or more of the techniques (e.g., methodologies) discussed hereinmay perform. Portions of this description may apply to the computingframework of various portions of the LCP device, the IMD, or theexternal programmer.

In alternative embodiments, the machine 700 may operate as a standalonedevice or may be connected (e.g., networked) to other machines. In anetworked deployment, the machine 700 may operate in the capacity of aserver machine, a client machine, or both in server-client networkenvironments. In an example, the machine 700 may act as a peer machinein peer-to-peer (P2P) (or other distributed) network environment. Themachine 700 may be a personal computer (PC), a tablet PC, a set-top box(STB), a personal digital assistant (PDA), a mobile telephone, a webappliance, a network router, switch or bridge, or any machine capable ofexecuting instructions (sequential or otherwise) that specify actions tobe taken by that machine. Further, while only a single machine isillustrated, the term “machine” shall also be taken to include anycollection of machines that individually or jointly execute a set (ormultiple sets) of instructions to perform any one or more of themethodologies discussed herein, such as cloud computing, software as aservice (SaaS), other computer cluster configurations.

Examples, as described herein, may include, or may operate by, logic ora number of components, or mechanisms. Circuit sets are a collection ofcircuits implemented in tangible entities that include hardware (e.g.,simple circuits, gates, logic, etc.). Circuit set membership may beflexible over time and underlying hardware variability. Circuit setsinclude members that may, alone or in combination, perform specifiedoperations when operating. In an example, hardware of the circuit setmay be immutably designed to carry out a specific operation (e.g.,hardwired). In an example, the hardware of the circuit set may includevariably connected physical components (e.g., execution units,transistors, simple circuits, etc.) including a computer readable mediumphysically modified (e.g., magnetically, electrically, moveableplacement of invariant massed particles, etc.) to encode instructions ofthe specific operation. In connecting the physical components, theunderlying electrical properties of a hardware constituent are changed,for example, from an insulator to a conductor or vice versa. Theinstructions enable embedded hardware (e.g., the execution units or aloading mechanism) to create members of the circuit set in hardware viathe variable connections to carry out portions of the specific operationwhen in operation. Accordingly, the computer readable medium iscommunicatively coupled to the other components of the circuit setmember when the device is operating. In an example, any of the physicalcomponents may be used in more than one member of more than one circuitset. For example, under operation, execution units may be used in afirst circuit of a first circuit set at one point in time and reused bya second circuit in the first circuit set, or by a third circuit in asecond circuit set at a different time.

Machine (e.g., computer system) 700 may include a hardware processor 702(e.g., a central processing unit (CPU), a graphics processing unit(GPU), a hardware processor core, or any combination thereof), a mainmemory 704 and a static memory 706, some or all of which may communicatewith each other via an interlink (e.g., bus) 708. The machine 700 mayfurther include a display unit 710 (e.g., a raster display, vectordisplay, holographic display, etc.), an alphanumeric input device 712(e.g., a keyboard), and a user interface (UI) navigation device 714(e.g., a mouse). In an example, the display unit 710, input device 712and UI navigation device 714 may be a touch screen display. The machine700 may additionally include a storage device (e.g., drive unit) 716, asignal generation device 718 (e.g., a speaker), a network interfacedevice 720, and one or more sensors 721, such as a global positioningsystem (GPS) sensor, compass, accelerometer, or other sensor. Themachine 700 may include an output controller 728, such as a serial(e.g., universal serial bus (USB), parallel, or other wired or wireless(e.g., infrared (IR), near field communication (NFC), etc.) connectionto communicate or control one or more peripheral devices (e.g., aprinter, card reader, etc.).

The storage device 716 may include a machine readable medium 722 onwhich is stored one or more sets of data structures or instructions 724(e.g., software) embodying or utilized by any one or more of thetechniques or functions described herein. The instructions 724 may alsoreside, completely or at least partially, within the main memory 704,within static memory 706, or within the hardware processor 702 duringexecution thereof by the machine 700. In an example, one or anycombination of the hardware processor 702, the main memory 704, thestatic memory 706, or the storage device 716 may constitute machinereadable media.

While the machine readable medium 722 is illustrated as a single medium,the term “machine readable medium” may include a single medium ormultiple media (e.g., a centralized or distributed database, and/orassociated caches and servers) configured to store the one or moreinstructions 724.

The term “machine readable medium” may include any medium that iscapable of storing, encoding, or carrying instructions for execution bythe machine 700 and that cause the machine 700 to perform any one ormore of the techniques of the present disclosure, or that is capable ofstoring, encoding or carrying data structures used by or associated withsuch instructions. Non-limiting machine readable medium examples mayinclude solid-state memories, and optical and magnetic media. In anexample, a massed machine readable medium comprises a machine readablemedium with a plurality of particles having invariant (e.g., rest) mass.Accordingly, massed machine-readable media are not transitorypropagating signals. Specific examples of massed machine readable mediamay include non-volatile memory, such as semiconductor memory devices(e.g., Electrically Programmable Read-Only Memory (EPROM), ElectricallyErasable Programmable Read-Only Memory (EEPROM)) and flash memorydevices; magnetic disks, such as internal hard disks and removabledisks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

The instructions 724 may further be transmitted or received over acommunications network 726 using a transmission medium via the networkinterface device 720 utilizing any one of a number of transfer protocols(e.g., frame relay, internet protocol (IP), transmission controlprotocol (TCP), user datagram protocol (UDP), hypertext transferprotocol (HTTP), etc.). Example communication networks may include alocal area network (LAN), a wide area network (WAN), a packet datanetwork (e.g., the Internet), mobile telephone networks (e.g., cellularnetworks), Plain Old Telephone (POTS) networks, and wireless datanetworks (e.g., Institute of Electrical and Electronics Engineers (IEEE)802.11 family of standards known as WiFi®, IEEE 802.16 family ofstandards known as WiMax®), IEEE 802.15.4 family of standards,peer-to-peer (P2P) networks, among others. In an example, the networkinterface device 720 may include one or more physical jacks (e.g.,Ethernet, coaxial, or phone jacks) or one or more antennas to connect tothe communications network 726. In an example, the network interfacedevice 720 may include a plurality of antennas to wirelessly communicateusing at least one of single-input multiple-output (SIMO),multiple-input multiple-output (MIMO), or multiple-input single-output(MISO) techniques. The term “transmission medium” shall be taken toinclude any intangible medium that is capable of storing, encoding orcarrying instructions for execution by the machine 700, and includesdigital or analog communications signals or other intangible medium tofacilitate communication of such software.

Various embodiments are illustrated in the figures above. One or morefeatures from one or more of these embodiments may be combined to formother embodiments.

The method examples described herein can be machine orcomputer-implemented at least in part. Some examples may include acomputer-readable medium or machine-readable medium encoded withinstructions operable to configure an electronic device or system toperform methods as described in the above examples. An implementation ofsuch methods may include code, such as microcode, assembly languagecode, a higher-level language code, or the like. Such code may includecomputer readable instructions for performing various methods. The codecan form portions of computer program products. Further, the code can betangibly stored on one or more volatile or non-volatilecomputer-readable media during execution or at other times.

The above detailed description is intended to be illustrative, and notrestrictive. The scope of the disclosure should therefore be determinedwith references to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

What is claimed is:
 1. A medical-device system, comprising: astimulation control circuit configured to generate a control signal todeliver cardiac stimulation to a heart of a patient according tostimulation parameters stored in a memory according to a plurality ofheart rate ranges, and to update at least a portion of the storedstimulation parameters, including: provide a plurality of timers eachhaving a duration, wherein each of the plurality of timers correspondsto different heart rate ranges, and is configured to expire after therespective duration has elapsed from a respective reset time; identify,from the plurality of heart rate ranges, a target heart range in which adetected heart rate falls, and measure an atrioventricular conductioncharacteristic value if the timer for the target heart range has expiredat the detected heart rate; and update at least a portion of thestimulation parameters stored in the memory and corresponding to thetarget heart rate range using the measured atrioventricular conductioncharacteristic.
 2. The system of claim 1, wherein the stimulationcontrol circuit is configured to reset the timer for the target heartrate range upon measuring the atrioventricular conduction characteristicvalue.
 3. The system of claim 1, wherein the stimulation control circuitis configured to select a stimulation parameter value from thestimulation parameters for a detected heart rate, the system comprisinga stimulator circuit configured to deliver cardiac stimulation using theselected stimulation parameter value.
 4. The system of claim 1, whereinthe stimulation timing parameters include atrioventricular delay (AVD)values, and the atrioventricular conduction characteristic includesintrinsic atrioventricular interval (AVI), and wherein the stimulationcontrol circuit is configured to generate a control signal to suspendventricular stimulation during the measurement of intrinsic AVI and toresume ventricular stimulation after the measurement of intrinsic AVI.5. The system of claim 1, further comprising a global timer having aduration, and the stimulation control circuit is configured to update atleast the portion of the stimulation parameters in response to anexpiration of the global timer.
 6. The system of claim 1, wherein thestimulation control circuit is configured to generate, in response tothe measurement of an atrioventricular conduction characteristic, acontrol signal to disable any subsequent measurement of atrioventricularconduction characteristic during a blanking period.
 7. The system ofclaim 1, wherein the stimulation control circuit is configured todetermine a stimulation parameter for the target heart rate range usingthe measured atrioventricular conduction characteristic scaled a weightfactor.
 8. The system of claim 7, wherein the stimulation controlcircuit is configured to update a stimulation parameter for the targetheart rate range using a weighted combination of a historicalstimulation timing parameter value and the measured atrioventricularconduction characteristic each scaled by respective weight factors. 9.The system of claim 1, wherein the stimulation control circuit isconfigured to determine or update the respective durations of theplurality of timers using information of prevalence of heart ratesdetected in the corresponding plurality of heart rate ranges.
 10. Thesystem of claim 1, wherein the stimulation control circuit is configuredto store in the memory a stimulation parameter table including thestimulation timing parameters and the corresponding plurality of heartrate ranges.
 11. The system of claim 1, wherein the stimulation controlcircuit is configured to: generate, and store in the memory, aregression model between (1) values of the atrioventricular conductioncharacteristic corresponding to a plurality of heart rate ranges and (2)the plurality of heart rate ranges; and estimate a value of theatrioventricular conduction characteristic at a specific heart rateusing the generated regression model.
 12. The system of claim 1, whereinthe stored stimulation parameters further correspond to atrial sensed(AS) events or atrial paced (AP) events at the plurality of heart rateranges, and the stimulation control circuit is configured to select theparameter for use during cardiac stimulation using information of a ASor AP event.
 13. The system of claim 1, wherein the stored stimulationparameters further include information of a pacing chamber configurationfor a plurality of heart rate or heart rate ranges, the pacing chamberconfiguration including a left-ventricular (LV) only pacing or abi-ventricular (BiV) pacing of both left and right ventricles, whereinthe stimulation control circuit is configured to select the LV-onlypacing or the BiV pacing using an atrioventricular interval or anatrioventricular interval variability at a detected heart rate.
 14. Amethod of operating a medical-device system to control cardiacstimulation using a plurality of timers corresponding to a plurality ofheart rate ranges, each of the plurality of timers configured to expireafter a respective duration has elapsed from a respective reset time,the method comprising: monitoring patient heart rates; identifying, fromthe plurality of heart rate ranges, a target heart range in which adetected heart rate falls; measuring an atrioventricular conductioncharacteristic value if a timer for the target heart range has expiredat the detected heart rate; and updating at least a portion of a setstimulation parameters stored in a memory and corresponding to thetarget heart rate range using the measured atrioventricular conductioncharacteristic; wherein the stimulation parameters include stimulationtiming parameters corresponding to the plurality of heart rate ranges.15. The method of claim 14, wherein storing the stimulation parametersincludes storing in the memory a stimulation parameter table thatincludes the stimulation timing parameters for atrial sensed (AS) eventsor atrial paced (AP) events and corresponding to the plurality heartrate ranges.
 16. The method of claim 14, wherein the stimulation timingparameters include atrioventricular delay (AVD) values, and theatrioventricular conduction characteristic includes intrinsicatrioventricular interval (AVI), and wherein the method comprising:generating a control signal to suspend ventricular stimulation duringthe measurement of intrinsic AVI; and after the measurement of intrinsicAVI, resuming ventricular stimulation and resetting the timer for thetarget heart rate range.
 17. The method of claim 14, comprising,subsequent to the measurement of intrinsic AVI, generating a controlsignal to disable any subsequent measurement of intrinsic AVI during ablanking period.
 18. The method of claim 14, comprising determining orupdating the respective durations for the plurality of timers usinginformation of prevalence of heart rates detected in the correspondingplurality of heart rate ranges.
 19. The method of claim 14, whereinupdating at least a portion of the stimulation parameters includes usinga weighted combination of a historical stimulation timing parametervalue and the measured atrioventricular conduction characteristic eachscaled by respective weight factors.
 20. The method of claim 14, furthercomprising selecting a stimulation parameter value from the stimulationparameters for a detected heart rate, and delivering cardiac stimulationvia a stimulator circuit using the selected stimulation parameter value.